Lung cancer is the leading cause of cancer deaths globally [1]. Patients with NSCLC, which accounts for over 80% of all the lung cancer cases, are often diagnosed at advanced stages of the disease, thus the prognosis of lung cancer remains poor [2]. With the development of advanced gene sequencing technology, the therapeutic strategy of NSCLC has been modified towards personalized therapy. Some specific driver genetic mutations have been identified in NSCLC, such as EGFR [3, 4], EML4-ALK fusion gene [5] and ROS fusion gene [6], which directs the development of molecular-targeted drug discovery of pharmaceutical industry and therapy for individual NSCLC patients. For example, gefitinib, which is also known as tyrosine kinase inhibitor (TKI), specifically inhibits EGFR and its downstream survival signaling pathway [7]. However, despite the initial significant responses to gefitinib treatment, like other chemotherapeutic agents, patients acquire resistance to gefitinib ultimately, and the median time to disease progression is just about 12 months [8]. Although the reason of drug resistance behind might be various, 49% of the resistance cases are associated with double mutations on EGFR L858R+T790M [8]. Therefore, there is an urgent need to identify EGFR crosstalk pathways and to discover more effective agents as candidate drugs for gefitinib-resistant NSCLC patients.
The investigation of ‘French Paradox’ which describes improved cardiovascular outcomes despite a high-fat diet in French people opens the study of resveratrol in many disorders and diseases [9-12]. Resveratrol is a polyphenol which wildly exists in grapes. It is a well-known chemopreventive and chemotherapeutic agent [13, 14]. The anti-cancer effect of resveratrol and its derivatives attracted mostly attentions. For example, DMU-212, a methoxylated trans-stilbene resveratrol analogue [15], has been testing in clinical trial. Many other derivatives and their use are still being investigated in lab.